Background. Globally,1.1 million infants die each year during the first four weeks of life due to prematurity.In the United States, prematurity is the second leading cause of infant mortality and the leading cause of infant mortality for African Americans. If birth could be delayed from 30 to 34 weeks gestation, the incidence of: inhospital mortality could be reduced from 8.1% to 0.4%;cerebral palsy could be reduced from 6.3% to 0.7%;and respiratory distress syndrome could be decreased from 44% to 3%. Delaying the birth of an infant <29 weeks gestation to term (= 37 weeks) is estimated to result in at least $122,000 savings/case. Treatment of preterm labor has focused on treating contractions rather than the long process of cervical ripening that precedes preterm labor. Pharmacologic agents to arrest preterm labor have functions to modify contracting smooth muscle not cervical ripening,5 and have failed to reduce preterm birth rates in the last 40 years. The long-term goal of this research program is to develop a noninvasive quantitative ultrasound (QUS) technique that will: detect early cervical ripening in humans;and lead to scientific interventions to modify preterm birth. The goal of this R21 application is to validate the biochemical, biomechanical and biostructural properties of cervical ripening with QUS, as an essential step to detect cervical ripening in humans. Aim 1. Determine the relationship among frequency-dependent QUS-derived parameters in the rat cervix as ripening occurs, with cervix tissue biochemical (collagen and water), biostructural (birefringence, histology, 3-D impedance map) biomechanical (stress-strain) properties. Aim 2. Determine the form factor that appropriately models pregnant cervix tissue. Methods. This is a prospective longitudinal repeated-measures experimental design consisting of 2 experiments to achieve aim 1 consisting of: a preliminary experiment (1) to determine sample size and a more definitive experiment (2). Experiment 3 will use 3-dimensional impedance modeling of a 3-dimensional histological data set to determine the form factor that appropriately models pregnant cervix tissue. Conclusion. We anticipate that the successful completion of this research will have furthered our goal of translating quantitative ultrasound of the cervix for use in humans by validating the biochemical (collagen and water), biostructural (birefringence, histology, 3-D impedance map) biomechanical (stress-strain) basis of quantitative ultrasound in the in vivo animal model. PUBLIC HEALTH RELEVANCE STATEMENT: The birth of a healthy baby at term is a universal expectation of prospective parents. However, 500,000 infants were born preterm in 2006. The underlying mechanisms preceding labor are not yet fully understood. The 21% increase in the incidence of preterm birth (to 12.8% of all births in 2006) in the United States between 1990 and 2006 is an indication of the seriousness of this problem. In 2006, 18.4% of African-American women, 14.2% of Native American women and 12.2% of Hispanic women delivered a preterm infant compared to 11.7% of White women. Preterm birth is the second leading cause (after congenital anomalies) of infant mortality in the United States and the leading cause of infant death among African-American infants.2 Compared with infants born full-term, premature infants born = 28 weeks gestation, have a one hundred-fold increase in the incidence of cerebral palsy (1/1000 infants born at term versus 100/1000 born premature). Delaying the birth of an infant <29 weeks gestation to term (= 37 weeks) is estimated to result in at least $122,000 savings/case. Reducing the preterm birth rate to 7% in the United States is a goal of the Healthy People 2010 initiative, and it is only by reducing the incidence of preterm birth that infant mortality in the United States can be addressed.